Experimental and theoretical studies have provided a framework for understanding protein folding, and computational advances have allowed millisecond-long simulations of specific folding pathways. However, experimental methods have not had the resolution to validate these pathways (see the Perspective by Sosnick and Hinshaw). Stigler et al. used ultrastable high-resolution optical tweezers to monitor at submillisecond resolution for tens of minutes the fluctuations of full-length calmodulin as it transitioned between unfolded and folded states. Lindorff-Larsen et al. used the supercomputer Anton and a single force field to simulate reversible folding and unfolding of 12 protein domains over periods ranging between 100 µs and 1 ms. The proteins, which represent the major structural classes (α helix, β sheet, and mixed αβ), folded to their experimentally determined structures by following a single dominant route in which the backbone adopted a native-like structure early in the folding process.